Treatment with hydroxyurea and tyrphostin-1 significantly improves the transduction efficiency of recombinant adeno-associated viruses in human cancer cells

Sung Jin Kim, Young Ran Nam, Ohkyu Shin, Jene Choi, Boyoung Lee, Jin Woo Chang, Yunhee Kim Kwon, Keerang Park, Heuiran Lee

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

To enhance the transduction efficiency (TE) of a recombinant adeno-associated virus 2 (rAAV2) in human cancer cells, we examined the combined effects of various chemicals known to influence the rAAV2 transduction process at distinct steps. Among the agents tested were trichostatin A, a histone deacetylase inhibitor, MG-132, a proteosome inhibitor, the genotoxic agents hydroxyurea, aphidicolin, etoposide and camptothecin, and tyrphostin-1, an epidermal growth factor receptor inhibitor. During or after chemical treatment, various human cancer cells were infected with rAAV2 expressing β-galactosidase. Treatment with hydroxyurea or etoposide plus tyrphostin-1 dramatically increased the TE in most cell lines. The combination of hydroxyurea plus tyrphostin-1 increased TE to 37.7±7.9%, 32.8±2.0% and 31.8±2.1% in SK-Hepl, HeLa, and HCT116 cells, respectively. In addition, following rAAV2 infection and treatment with hydroxyurea plus tyrphostin-1, long-term transgene expression was observed for up to 6 months, with no damage to the transduced cells. These results indicate that rAAV2 transgene expression can be significantly enhanced by a combination of chemical agents with distinct activity and prolonged gene expression can occur following rAAV2 gene transfer into human cancer cells.

Original languageEnglish
Pages (from-to)1475-1479
Number of pages5
JournalOncology reports
Volume14
Issue number6
DOIs
Publication statusPublished - 2005 Dec

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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